Background: The Quality of Life (QOL) questionnaire version I consisted of 38 items that were validated using 392 patients. The experiences gained through the interaction with the patients during the administration of the questionnaire provided a lot of inputs for the improvization of the tool. Aim: The current study is aimed at certain modifications of the QOL questionnaire version I and standardization of the same. Materials and Methods: The modifications of version I QOL scale included the change of verbatim, splitting, deleting, and adding of new items. Finally, version II included 42 items. It was administered to 183 cancer patients irrespective of their demographic details for further standardization. Statistics: The principal component method with varimax rotation was used. Spearman′s product moment correlation and Cronbach′s alpha coefficient were used for reliability analysis. Results: The data were subjected to factor analysis to explore the factors. Eleven factors emerged with the eigenvalue ranging from 8.03 to 1.10 and accounted for 66.7% variance. The first factor contributed maximally, 19.5%, and the remaining 10 factors contributed a total of 46.2% variance on QOL. They are general well-being, physical well-being, psychological well-being, familial relationship, sexual and personal ability, cognitive well-being, optimism and belief, economical well-being, information support, patient-physician relationship, and body image. The Cronbach alpha of 0.90 and split-half reliability of 0.80 indicated a high reliability of the tool. Conclusion: The factor structure showed that QOL is a multidimensional concept having different aspects. The Cancer Institute QOL Questionnaire version II for cancer patients is found to be a valid and reliable tool and feasible to administer at the clinical settings.